This proposal will continue to probe the complexity of immunologic mechanisms in the human respiratory tract, by first analyzing immune components in the lungs of normal subjects, asymptomatic cigarette smokers and nonsmokers, and then comparing these findings with those found in patients with forms of interstitial lung disease (idiopathic pulmonary fibrosis, sarcoidosis and hypersensitivity pneumonitis) and cystic fibrosis. The overall aim is to dissect the inflammatory reaction that is occurring in diseased lungs and in so doing better understand pathogenetic mechanisms and devise more effective forms of therapy. The general approach is to collect upper respiratory tract secretions (nasal washing and parotid fluid) and lower airway fluid by bronchoalveolar lavage (BAL) and then analyze these specimens for a variety of immunoglobulins and proteins and for cells; comparisons are made with blood values. An underlying theme of this investigation is to assess the role of immunoglobulins in the lung, especially that of IgG and its 4 distinct heavy chain subclasses. Projects in the grant relate to: quantitation of IgG subclasses in BAL fluid, functional activity of individual subclasses (alveolar macrophage receptor binding and stimulation of chemotactic factors), opsonic antibody activity in cystic fibrosis, enumeration of lung B-lymphocytes and plasma cells that secrete specific IgG subclass immunoglobulin, and characterization of indigenous lung proteins. The basic immunologic methods to be used will combine immunochemical analysis and in vitro functional activity of cultured respiratory and blood cells. The projected results should uncover more details about fundamental respiratory immunity in normals and should help unravel immune injury mechanisms in some important lung diseases that will sharpen the approach to therapy and provide insight into etiology.